This invention relates to hydroxy and alkoxy substituted pyrimidines, more particularly, 2-amino 2-thio, 2-substituted amino and 2-substituted thio-4-substituted-5-(hydroxy or alkoxy) pyrimidines which are optionally 6-substituted, acyl derivatives thereof pharmaceutical compositions containing such compounds as active ingredients and methods of treatment with such compounds. Some hydroxy compounds from which the compounds of the present invention may be prepared and that are inhibitors of leukotriene synthesis are disclosed in European Patent Application publication No. 210 044.
Bray et al., in Biochem. J., 48, 400 (1951), describe 2-amino-4,6-dimethyl-5-hydroxypyrimidine and its preparation without disclosing any pharmaceutical or other utility.
Dubovenko et al., in Chemical Abstracts, 94: 121446z (1981), describe 2-dimethylamino-4,6-diphenyl-5-hydroxypyrimidine and its preparation without disclosing any pharmaceutical or other utility.
Chesterfield et al., in J. Chem. Soc., 4595, (1960), describe 4,6-dimethyl-5-hydroxy-2-thiopyrmidine and its preparation without disclosing any pharmaceutical or other activity.
Esanu et al., in U.K. Patent Application No. 2045756, disclose 2-isopropylamino-5-hydroxypyrimidine for the treatment of muscular dystrophy. This prior-published application does not disclose any substitution of the mentioned compound at the 4-and 6-positions of the pyrimidine group.
LaMattina, in U.S. Pat. No. 4,554,276, assigned to the same assignee as the present application, discloses 2-amino-4-methyl-5-hydroxypyrimidines having similar pharmaceutical utilities as the compounds of the present invention.
Walker et al., in U.S. Pat. No. 4,711,888, assigned to the same assignee as the present application, disclose 2-amino-4 substituted-5-(hydroxy or alkoxy)-pyrimidines, which may be 6-substituted, and derivatives thereof having similar pharmaceutical activities as the compounds of the present invention.
Walker et al., in PCT Application PCT/US 87/03171, filed Dec. 2, 1987 and also assigned to the same assignee as the present application, disclose acyl derivatives of 2-amino-4-substituted-5-hydroxy pyrimidines, which may be 6-substituted, and derivatives thereof having similar pharmaceutical activities as the compounds of the present invention.
Current treatment of asthma focuses on the relief of acute bronchospasm through the use of bronchodilators. It is thought that acute bronchospasm is only an overt manifestation of chronic inflammation. Leukotrienes may play a role both in the bronchospasm and the chronic inflammation. They are known to be potent vasodilators and chemotactic agents. They are also produced in allergic reactions and bring about slow contraction of lung tissue in vitro. An inhibitor of leukotriene synthesis should therefore be of use in the treatment of asthma and other pulmonary diseases.
Chronic gastric and duodenal ulcers, together known as peptic ulcers, are the subject of a variety of treatments, including special diets, drug therapy and surgery, depending upon the severity of the condition. Particularly valuable therapeutic agents useful for the treatment of gastric hyperacidity and peptic ulcers are the histamine-H.sub.2 receptor antagonists, which block the action of the physiologically-active compound histamine at the H.sub.2 -receptor sites in the animal body and thereby inhibit the secretion of gastric acid.